Current Pharmaceutical Biotechnology - Volume 20, Issue 8, 2019

Objective: Catheter-related bloodstream infections (CRBSIs) pathogenesis is complex and multifactorial mostly due to cutaneous microorganisms migration through the catheter insertion site and catheter tip colonization. Ochrobactrum anthropi is a gram-negative bacterium belonging to the Brucellaceae and related infections are especially observed in immunocompromised patients. Methods: Therefore, O. anthropi infection prevention and surveillance are relevant issues for healthcare system and risk management, in order to improve healthcare quality and patient safety. Four cases of anthropi-related CRBSIs occurring in immunodepressed patients under chemotherapy treatment are reported and the possible prevention and surveillance strategies are analyzed. Results: In the reported cases, all infections occurred almost simultaneously in the Oncology Unit, leading to hypothesize an identical infection source. Subsequently, a clinical audit was performed in order to investigate infection origin and implement prevention and control strategies. Clinical audit allowed to identify the hand hygiene defects as the primary source of the infections, responsible for catheter flushing solution contamination. Conclusion: The aim of this study is to reveal how through correct root cause analysis and clinical audit, several measures could be undertaken in order to promote the prevention of the CRBSIs risk.

Background: The phenomenon of clinical negligence claims has rapidly spread to United States, Canada and Europe assuming the dimensions and the severity of a pandemia. Consequently, the issues related to medical malpractice need to be studied from a transnational perspective since they raise similar problems in different legal systems. Methods: Over the last two decades, medical liability has become a prominent issue in healthcare policy and a major concern for healthcare economics in Italy. The failures of the liability system and the high cost of healthcare have led to considerable legislative activity concerning medical malpractice liability, and a law was enacted in 2012 (Law no. 189/2012), known as the “Balduzzi Law”. Results: The law tackles the mounting concern over litigation related to medical malpractice and calls for Italian physicians to follow guidelines. Briefly, the law provided for the decriminalisation of simple negligence of a physician on condition that he/she followed the guidelines and “good medical practice” while carrying out his/her duties, whilst the obligation for compensation, as defined by the Italian Civil Code, remained. Judges had to consider that the physician followed the provisions of the guidelines but nevertheless caused injury to the patient. Conclusion: However, since the emission of the law, thorny questions remain which have attracted renewed interest and criticism both in the Italian courts and legal literature. Since then, several bills have been presented on the topic and these have been merged into a single text entitled “Regulations for healthcare and patient safety and for the professional responsibility of healthcare providers”.

Background: Healthcare Associated Infections (HAIs) represent a crucial issue in health and patient safety management due to the persistent nature, economic impact and possible preventability of the phenomenon. Compensation claims for damages resulting from HAI could provide insights that can improve the understanding of suboptimal steps in the therapeutic process, enable an estimate of costs related to infectious complications, and guide the development of planning tools for implementation of the quality of care. Objective: This paper analyzes all the HAI claims received at the Umberto I General Hospital of Rome across a five-year period with the aim of outlining a methodological approach to the litigation management and of characterizing the economic impact of infections on health facilities resources. Methods: All claims received during the study period have been classified according to the International Classification for Patient Safety (ICPS) system. Subsequently, claims related to Healthcare Associated Infections were evaluated through an innovative tool for determination of the risk of loss, the Advanced Loss Eventuality Assessment (ALEA) score. Results: The results obtained demonstrate the relevance of a correct management of HAI claims in the administration of a health care system. Specifically, the cases examined during the study highlighted the significant impact of infectious diseases of a nosocomial nature in terms of frequency and economic exposure. Conclusion: The proposed methodological approach allows a productive analysis of the internal processes, providing fundamental data for the refinement of the preventive strategies and for the rationalization of the resources through the expenditure forecasts. Article Highlights Box: Healthcare-Associated Infections represent an essential element to consider in the management of health facilities. • Many studies highlight the economic burden of Healthcare-Associated Infections in health policies. • Litigation management represents a useful resource in the prevention of Healthcare Associated Infections. • Appropriate clinical risk management policies in the field of Healthcare-Associated Infections allow the implementation of preventive measures, the reduction of the incidence of the phenomenon and the quality of care. • The costs of Healthcare-Associated Infections can be limited through a systematic methodological approach based on Advanced Loss Eventuality Assessment and technical estimate of the value of each case. • The application of a standardized system would be desirable in any health facility despite the potential methodological, technical, behavioral and financial issues.

Background: Healthcare quality improvements are one of the most important goals to reach a better and safer healthcare system. Reviewing in-hospital mortality data is useful to identify areas for improvement, and to monitor the impact of actions taken to avoid preventable cases, such as those related to healthcare associated infections (HAI). Methods: In this paper, we present the experience of the Mortality Committee of Bambino Gesù Children Hospital (OPBG). OPBG has instituted a process of systematic revision of all in-hospital deaths conducted by a multidisciplinary team. The goal is to identify system-wide issues that could be improved to reduce in-hospital preventable deaths. In this way, the mortality review goes alongside all the other risk management activities for the continuous quality improvement and patient safety. Results: In years 2008-2017, we performed a systematic analysis of 1148 inpatient deaths. In this time period, the overall mortality rate was 0.4%. Forty-seven deaths were caused due to infections, 10 of which involved patients with HAI transferred to OPBG from other facilities or patients with community- acquired infections. Six deaths related to HAI were followed by claims compensations. All these cases were not followed by compensation because the onset of HAI was considered an inevitable consequence of the underlying disease. Conclusion: Introduction of the mortality review committee has proved to be a valid instrument to improve the quality of the care provided in a hospital, allowing early identification of care gaps that could lead to an increase in mortality rates. Article Highlights Box: Reduction of preventable deaths is one of the most important goals to be achieved for any health-care system and to improve the quality of care. • Several studies have shown that analysis of morbidity and mortality rate helps to detect any factors that can lead to an increase in in-hospital mortality rates. • The review of in-hospital deaths allows to learn how to improve the quality and safety of care through identification of critical issues that lead to an increase in mortality ratio. • In some medical areas, such as intensive care units or surgery, the implementation of the conference on mortality and morbidity is more useful for assessing procedures at high risk of errors. • The implementation of existing databases with data deriving from the systematic review of medical records and in-hospital deaths appears to be desirable. • Mortality Review Committees can represent a very useful tool for all the health facilities for the reduction of preventable deaths, such as those related to HAI.

Background: The increasing antimicrobial resistance poses a challenge to surveillance systems and raises concerns about the impact of multidrug-resistant organisms on patient safety. Objective: The study aimed to estimate extra hospital stay and economic burden of infections due to alert organisms - mostly multidrug-resistant - in a teaching hospital. Methods: The present retrospective matched cohort study was conducted based on the analysis of hospital admissions at Sant’Andrea Teaching Hospital in Rome from April to December 2015. Extra hospital stay was the difference in the length of stay between each case and control. All the patients developing an infection due to an alert organism were considered cases, all others were eligible as controls. The costs of LOS were evaluated by multiplying the extra stay with the hospital daily cost. Results: Overall, 122 patients developed an infection due to alert organisms and were all matched with controls. The attributable extra stay was of 2,291 days (mean 18.8; median 19.0) with a significantly increased hospitalization in intensive care units (21.2 days), bloodstream infections (52.5 days), and infections due to Gram-negative bacteria (mean 29.2 days; median 32.6 days). Applying the single day hospital cost, the overall additional expenditure was 11,549 euro per patient. The average additional cost of antibiotic drugs for the treatment of infections was about 1,200 euro per patient. Conclusion: The present study presents an accurate mapping of the clinical and economic impact of infections attributable to alert organisms demonstrating that infections due to multidrug-resistant organisms are associated with higher mortality, longer hospital stays, and increased costs. Article Highlights Box: The increasing antimicrobial resistance poses a challenge for surveillance systems and raises concerns about the impact of multidrug-resistant organisms on patient safety. • Healthcare-associated infections (HAIs) have historically been recognized as a significant public health problem requiring close surveillance. • Despite several and reliable findings have been achieved on clinical issues, our knowledge on the economic impact of healthcare-associated infections due to multidrug-resistant organisms needs to be widened. • Estimating the cost of infections due to multidrug-resistant organisms in terms of extra hospital stay and economic burden is complex, and the financial impact varies across different health systems. • Evaluations of social and economic implications of hospital infections play an increasingly important role in the implementation of surveillance systems. • The costs of infection prevention and control programs and dedicated personnel are relatively low and self-sustainable when efficient.

Background: Healthcare-associated infections are one of the most serious Public Health concern, as they prolong the length of hospitalization, reduce the quality of life, and increase morbidity and mortality. Despite they are not completely avoidable, the number of healthcare-associated infections related to negligence claims has risen over the last years, contributing to remarkable economic and reputation losses of Healthcare System. Methods: In this regard, several studies suggested a key role of medical records quality in determining medical care process, risk management and preventing liability. Clinical documentation should be able to demonstrate that clinicians met their duty of care and did not compromise patient’s safety. Results: Therefore, it has a key role in assessing healthcare workers’ liability in malpractice litigation. Our risk management experience has confirmed the role of medical records accuracy in preventing hospital liability and improving the quality of medical care. Conclusion: In the presented healthcare-associated infections cases, evidence-based and guidelinesbased practice, as well as a complete/incomplete medical record, have shown to significantly affect the verdict of the judicial court and inclusion/exclusion of hospital liability in healthcare-associated infections related claims.

Background: Healthcare-associated infections (HCAIs) occur when patients receiving treatment in a health care setting develop an infection. They represent a major public health problem, requiring the integration of clinical medicine, pathology, epidemiology, laboratory sciences, and, finally, forensic medicine. Methods: The determination of cause of death is fundamental not only in the cases of presumed malpractice to ascertain the causal link with any negligent behavior both of health facilities and of individual professionals, but also for epidemiological purposes since it may help to know the global burden of HCAIs, that remains undetermined because of the difficulty of gathering reliable diagnostic data. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insult, is mandatory in HCAIs related deaths. Results: Important tasks for forensic specialists in hospitals and health services centers are the promotion of transparency and open communication by health-care workers on the risk of HCAIs, thus facilitating patients’ engagement and the implementation of educational interventions for professionals aimed to improve their knowledge and adherence to prevention and control measures. Conclusion: HCAIs are a major problem for patient safety in every health-care facility and system around the world and their control and prevention represent a challenging priority for healthcare institution and workers committed to making healthcare safer. Clinicians are at the forefront in the war against HCAIs, however, also forensic pathologists have a remarkable role.

Background: One of the most prevalent cancers befell to women is considered to be breast cancer (BC). It is also the deadliest among the female population after lung cancer. Additionally, several studies have demonstrated that there is an association between microRNA34-a and breast cancer. Methods: We searched PubMed, Web of Science, and Google Scholar up to December 2018. Those studies which have been studied miR-34a and its tumor-suppressing capabilities were considered as the most important topics. Moreover, we extracted articles which were solely focused on microRNA-34a in breast cancer therapy. Finally, 80 articles were included. Results: In comparison with the normal tissues, down-regulation of miR-34a expression is shown considerably in tumor cells. Overexpression of miR-34a acts as a tumor suppressor by transcriptional regulating one of the signaling pathways (TP53), NOTCH, and transforming growth factor beta (TGF-β), Bcl- 2 and SIRT1genes, HDAC1 and HDAC7, Fra-1, TPD52, TLR Via CXCL10. Moreover, drug resistance declines which lead to the apoptosis, cell cycle arrest and senescence. As a result, the proliferation, invasion and metastasis of the tumor are suppressed. The Mrx34 drug contains miR-34a mimic and a lipid vector. MiR-34a as the active ingredient portrays the role of a tumor suppressor. This drug has recently entered the clinical trials studies. Conclusion: These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond.

Background: The ensemble building is a common method to improve the performance of the model in case of regression as well as classification. Objective: In this paper we propose a weighted average ensemble model to predict the number of incidence for infectious diseases like typhoid and compare it with applied models for prediction. Methods: The Monthly data of dengue and typhoid cases from 2014 to 2017 were taken from integrated diseases surveillance programme, Government of India. The data was processed by three regressions such as support vector regression, neural network and linear regression. Results: To evaluate the prediction error and compare it with different models, different performance measures have been used such as MSE, RMSE and MAE and it was found that proposed ensemble method performed better in terms of forecast measures. Conclusion: Our main aim in this paper is to minimize the prediction error; the resulting proposed weighted average ensemble model has shown a significant result in terms of prediction errors.

Objective: In the present study, Solenostemma argel effervescent tablets were prepared from Argel methanolic extract. Methods: The tablets were examined for their ability to impede carbon tetrachloride (CCl4)-induced lipid peroxidation in mice liver. The antioxidant activities of the enzymes; super-oxide dismutase (SOD), glutathione peroxidase (GS-PX) along with malondialdehyde level were tested in liver tissues. Results: The obtained results indicated that the antioxidant enzyme activities were remarkably reduced while the level of Malondialdehyde (MDA), which shows lipid peroxidation, and the activity of alanine aminotransferase (a liver function test) were remarkably intensified following intra-peritoneal i.p injection with the single sub-lethal hepatotoxic dose of CCl4 compared to the control. A necrotic lesion in the liver of mice injected with CCl4 was observed by the histopathological examination. The damaging influence of CCl4 was improved by the retreatment with Argel or BHT, which could also be observed in the normal appearance of the liver tissue. Conclusion: In this study, it was concluded that S. Argel and butylated hydroxytoluene (BHT) could be effective by decreasing lipid peroxidation and increasing the activities of antioxidant enzymes. Therefore, Argel might be applied as a hepatoprotective agent without any side effects.